1. Field of the Invention
The present invention relates to a process for producing porous polymer materials and, more particularly, to a process for producing porous polymer materials which are used in biomedical engineering.
2. Description of the Prior Art
Recently, with the development of biotechnology, biomedical materials are combined with a technology of tissue or cell culture in order to develop a new research field in tissue engineering. A very important key technology in the tissue engineering is to develope a biodegradable porous material substrate. The tissue or cell attaches and grows on the three-dimensional structure of the porous material. As the tissue or cell is grown, the porous material is degraded and absorbed. Finally, the implanted cell and the composite substrate replace the tissue defection region and become part of the human body. In order to germinate the cell in porous materials, porous materials are developed with the following characteristics:
(1) capable of being absorbed and degraded;
(2) high porosity;
(3) suitable pore size;
(4) three-dimensional porous structure; and
(5) interconnecting pores.
In the character of absorption, the biodegradable polymer materials, such as polyglycolide(PGA), polylactide (PLA), poly (lactide-co-glycolide) (PLGA), polycaprolactone, polydioxanone and polyorthoester, are most valuable at the present time. These polymer materials could be degraded into small molecular chains in organism. The products would be excreted out of human body via a metabolism process. Therefore, the degraded products will not be remained in human body.
As to the development of the tissue engineering technology, there are several processes to prepare the biodegradable porous polymer materials in recent years. Conventional methods for preparing the porous polymer materials are classified as follows:
1. solution casting;
2. solvent-casting particulate leaching;
3. gel casting;
4. gas saturation;
5. phase separation;
6. bonded fiber; and
7. particle sintering.
The phase separation method is frequently mentioned. The major principle of the phase separation method includes mixing two liquids which are insoluble in each other, such as aqueous solution and polymer solution, congealing the mixture in freeze, putting it into a copper vessel and freeze-drying to suck all of the aqueous solution out of the vessel. Finally, the porous polymer material is formed after drying in vacuum at room temperature for seven days. The advantage of this method resides in forming porous materials with high porosity (about 90 vol %) and interconnecting pores. The pore size and the porosity are controlled by the amount of the aqueous solution. However, the mixture is solidified by congealing in freeze and the pore morphology is influenced by the shape of congealing ice crystal. The technology of controlling the shape of ice crystal and the uniformity of particle size are not matured until now and still need to be improved. Moreover, the porous materials formed by phase separation method need to be dried in vacuum by using the freeze dryer. The cost is expensive and the size of porous materials is not easy to be magnified. These are disadvantage to mass production.
Except the phase separation method, the bonded fiber method and the particle sintering method are commonly used for preparing porous polymer materials. The theorem of these two methods is that the polymer fiber or particles are coagulated to each other by physical heating to form a three-dimensional structure. According to the recently published processes, the polymer bonded fiber method needs more than two polymers and solvents, and the procedures are complicated and disadvantageous for mass production. In the particle sintering method, the porosity formed after the particles are coagulated by sintering is low, and the pore size is too small to be practicable. Moreover, the common defect of these two methods is that the materials are coagulated by heating treatment. The polymer materials would probably decompose during the heating treatment, and the original characteristics of the polymer materials would be destroyed.
As to the polymer manufacture, the solution casting method and the solvent-casting particulate leaching method are more traditional and had been researched for a longer time than other methods.
The solution casting method comprises dissolving a polymer in a solvent, shaping in the mold and separating the solvent out by suction or washing to form a porous structure. The pores formed with this method are apparently small, and the pore size normally below 50 micrometers. Besides, the solution casting method can only produce thin membranes and can hardly fabricate three-dimensional bulk articles. Adding soluble salts in the solution casting method and leaching the salts out is called the solvent-casting particulate leaching method, which is capable of producing porous structure with larger pore size.
In the solvent-casting particulate leaching method, the degradable polymer is dissolved in a solvent to form a polymer solution and the polymer solution is mixed with a soluble salt. Then, the mixture is poured into a non-solvent which can not dissolve the degradable polymer (such as water or methanol) in order to precipitate the polymer. Alternatively, the solvent might as well be removed by vacuum suction. A substantial amount of water is subsequently introduced into the materials to wash the soluble salt and to form massive interconnecting pores. The advantages of this method are that the method is simple in operation and, the pore size and the porosity of the materials are easily controlled by the amount and the particle size of the added salt. However, due to the density difference between the liquid polymer solution and the solid salt, the distribution of the soluble salt is not uniform in the polymer solution. Moreover, the polymer solution and the soluble salt particles are respectively mixed in a liquid state and a solid state so that the salt particles are wrapped by the polymer solution. When the polymer are precipitated from water or the solvent is sucked out, the wraped salt can not be washed out and still remains in the final porous materials. Additionally, a solidified layer is formed on the outer layer of the polymer when the polymer is precipitated or the solvent is sucked out. The solidified layer will inhibit the outside water to get into the material and the inside solvent to be sucked out from the material. Consequently, the inside salt will not be washed out and the organic solvent will remain inside the materials. Therefore, most of the porous materials, prepared by solvent-casting particulate leaching, have a limitation of thickness, i.e., only thin articles such as membrane could be made. Lamination of several layers of membrane is normally applied if a three-dimensional bulk article is desired.
To overcome the above disadvantages of the prior art, the present invention provides a novel and effective method for producing porous polymer materials.
The present invention provides a process for rapidly and massively producing porous polymer materials which have high porosity and interconnecting pores.
The present invention provides a novel process for producing a porous polymer material to overcome the disadvantages of the solvent-casting particulate leaching method. According to the solvent-casting particulate leaching method, the major disadvantage of preparing the three-dimensional substrate is unable to precipitate the polymer material and introduce water into the material deeply to wash the salts out. Therefore, the present invention uses a pressure difference while forming the porous polymer matrix and washing the salts out. The pressure difference is used to introduce water into the materials to precipitate the polymer and wash the salt particles out.
Only the pressure difference cannot introduce water into the liquid polymer solution. Therefore the polymer material of the present invention is not mixed with salt particles after being dissolved in an organic solvent, but directly mixed with salt particles in its solid state. The mixture is placed into an apparatus which can be introduced a liquid and a pressure difference. A solvent is introduced through the mixture of the polymer material and the salt particles to dissolve and fuse the surface of the polymer materials. A pressure difference is used to suck a surplus solvent. A non-solvent is then introduced through the partially dissolved polymer material to precipitate and solidify the partially dissolved polymer parts. Finally, a substantial amount of water is used to wash the inside salt particles out so as to form a porous structure.
In one embodiment of the present invention, the polymer particles and the salt particles are mixed in their solid states. Therefore, the mixed particles have a massive space between particles and could be introduced with a solvent and a non-solvent deeply. The polymer material not only has porous structure formed after the salt particles are dissolved, but also has interconnecting channels formed after the non-solvent and water pass through the space within the particles. The process of the present invention can manufacture a high porosity three-dimensional structure with interconnecting pores and rapidly produce the porous polymer materials in large size.
In comparison with conventional technologies, the process of the present invention is quicker and easier. Besides, the water can pass through the inside of the materials massively and deeply, and no salt particles and solvent residual are left. The porosity and pore size of the resulted substrate are controlled by the ratio and the particle size of the added salt particles. In the future, the substrates with different porosity and pore size can be prepared in accordance with different requirements. Moreover, the size of the porous polymer materials depends on the vessel of the apparatus, such as a leach. The larger the vessel is used, the larger the volume of the three-dimensional porous polymer material is formed. The present invention is beneficial in mass production because the disadvantages of conventional technologies are overcome.